ABSTRACT Pulmonary hypertension (PH) is a highly debilitating disease that affects about 1% of the global population, which increases up to 10% in individuals aged more than 65 years. The life expectancy for these patients is less than 10 years after diagnosis, and no specific drugs are available for pharmacologic treatment. Despite the introduction PDE5, prostacyclin analogs, and endothelin antagonists, mortality remains high and quality of life poor. Therefore, inhalation and aerosolization are the best options for administering drugs to treat/manage PH. In this context, inhaled nitric oxide (iNO), a pulmonary-specific vasodilator, has been shown to be the best option for treating PH without compromising systemic blood pressure. Current iNO therapy requires a complex and expensive (approximately $180/hour) system of gaseous NO storage cylinders, transportation, and devices to monitor and regulate the dilution and delivery of NO, O2, and nitrogen dioxide (NO2). Therefore, this therapy is only in intensive care units and operating rooms of established hospitals in developed countries. Consequently, the demand is high and the opportunity large for new, inexpensive technologies that are less complex and portable for use in and out of hospitals. Since 1999, when the FDA approved the use of iNO therapy, several start- up companies have worked to develop such devices, but none has yet reached the market. We intend to fill this gap with our technology. Low molecular weight S-nitrosothiols (SNO) can be generated easily by reacting acidified nitrite with thiols in the laboratory. These SNO are not stable and spontaneously decompose to NO and corresponding disulfides. Hence these SNO have special ability to store and release NO. Our idea is to use this NO as a source of iNO therapy. Our preliminary studies indicate that NO released from S-nitrosothiols can be removed successfully from the reaction vessel and then introduced into carrier gas. Manipulating the reaction conditions can sustain this NO for over 10 hours. The main goal of the phase 1 study is to build prototype portable devices and then evaluate the purity of NO gas, as these are major hindrance to developing any novel inhaled technologies and FDA approval. Nitrogen dioxide (NO2) that forms as result of NO reaction with carrier gas, oxygen is a major toxic contaminant, especially in noninvasive iNO therapy. This NO2 formation will be minimized by generating desired levels of NO (NO2 formation is favored at higher NO concentrations) under anaerobic conditions and deliver to patients without storage. NO2 formation will be measured at the pre-set and lung level by direct and indirect methods via chemiluminescence assay and electrochemical sensors, respectively. A benchtop noninvasive iNO delivery system that simulates iNO delivery to patients will be used to evaluate the purity of gas and function of devices. Establishing the purity of gas and prototype device functions are an imperative before investing time and money in developing a final full-scale product. In summary our technology will deliver sustained, tunable levels of iNO with portability, increased safety (minimum or none toxic gases), less expensively, without the use of bulky cylinders.